Hydrochloric Acid → 6-(4-{5-[(4-fluorophenyl)methyl]-6-methylpyrimidin-4-yl}-2,3,4,5-tetrahydro-1,4-benzoxazepin-7-yl)-1H-imidazo[4,5-b]pyridin-2-amine

HRID 241195노트

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HRID 241195 반응식
[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9]2[C:10]([N:16]3[CH2:22][C:21]4[CH:23]=[C:24]([C:27]5[CH:28]=[C:29]6[NH:35][C:34]([NH:36]C(=O)OC)=[N:33][C:30]6=[N:31][CH:32]=5)[CH:25]=[CH:26][C:20]=4[O:19][CH2:18][CH2:17]3)=[N:11][CH:12]=[N:13][C:14]=2[CH3:15])=[CH:4][CH:3]=1.Cl>CO.[OH-].[K+]>[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9]2[C:10]([N:16]3[CH2:22][C:21]4[CH:23]=[C:24]([C:27]5[CH:28]=[C:29]6[NH:35][C:34]([NH2:36])=[N:33][C:30]6=[N:31][CH:32]=5)[CH:25]=[CH:26][C:20]=4[O:19][CH2:18][CH2:17]3)=[N:11][CH:12]=[N:13][C:14]=2[CH3:15])=[CH:4][CH:3]=1

참가 물질

5

반응물 2

HCID 313Hydrochloric AcidHCID 59586590methyl[6-(4-{5-[(4-fluorophenyl)methyl]-6-methylpyrimidin-4-yl}-2,3,4,5-tetrahydro-1,4-benzoxazepin-7-yl)-1H-imidazo[4,5-b]pyridin-2-yl]carbamate

생성물 1

HCID 595861736-(4-{5-[(4-fluorophenyl)methyl]-6-methylpyrimidin-4-yl}-2,3,4,5-tetrahydro-1,4-benzoxazepin-7-yl)-1H-imidazo[4,5-b]pyridin-2-amine수율 67%

시약·촉매·용매 2

HCID 887Methanol용매HCID 14797Potassium Hydroxide용매

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온도
65 °C

실험 절차

A mixture of methyl [6-(4-{5-[(4-fluorophenyl)methyl]-6-methylpyrimidin-4-yl}-2,3,4,5-tetrahydro-1,4-benzoxazepin-7-yl)-1H-imidazo[4,5-b]pyridin-2-yl]carbamate (15 mg, 0.028 mmol) in methanol and 2 M aqueous potassium hydroxide (1:1, 2 mL) was stirred at 65° C. for 18 hours. The reaction mixture was cooled, adjusted to pH 10 with 2 N hydrochloric acid, concentrated, diluted with ethyl acetate (10 mL), washed with brine solution (5 mL), dried over sodium sulfate, filtered and concentrated. The residue was purified by preparative reverse phase HPLC to give 6-(4-{5-[(4-fluorophenyl)methyl]-6-methylpyrimidin-4-yl}-2,3,4,5-tetrahydro-1,4-benzoxazepin-7-yl)-1H-imidazo[4,5-b]pyridin-2-amine (8.9 mg, 67% yield). 1H NMR (400 MHz, DMSO-D6): 8.46 (1H), 8.02 (br, 1H), 7.47 (d, 1H), 7.39 (dd, 1H), 7.10 to 6.96 (m, 5H), 7.75 (br, 1H), 4.53 (s, 2H), 4.30 (m, 2H), 4.00 (s, 2H), 3.89 (m, 2H), 2.22 (s, 3H), MS (EI) for C27H24FN7O: 428 (MH+).

후처리

  1. temperatureThe reaction mixture was cooled
  2. concentrationconcentrated
  3. additiondiluted with ethyl acetate (10 mL)
  4. washwashed with brine solution (5 mL)
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was purified by preparative reverse phase HPLC

출처 및 근거

ORD 기록
ord-dac38d1aaaf9413ea67fd156210765ac
출처 데이터셋
uspto-grants-2014_02
특허 번호
US08648066B2

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